A study led by the CBGP unravels a key weapon superbugs use to destroy antibiotics

In 2001, a next-generation superbug weapon, the KPC-2 enzyme, was detected for the first time in a hospital in North Carolina. This enzyme is capable of rendering almost all antibiotics in the beta-lactam family useless, which includes well-known drugs such as penicillin and amoxicillin, as well as "last-resort" compounds such as carbapenems. In less than a decade, KPC-2 had spread across the planet, causing outbreaks with mortality rates exceeding 40% and a massive health impact, marked by prolonged hospitalizations and expensive treatments. The secret: KPC-2's ability to jump between bacteria and its surprising ability to reinvent itself in the face of new antibiotics.

The research group, led by Galician CBGP researcher Alejandro Couce, based at the Polytechnic University of Madrid, decided to reproduce this process in the laboratory to observe, step by step, how the KPC-2 enzyme learns new tricks. The work has been published in the prestigious journal Nature Ecology & Evolution, a leading reference for the best science in these disciplines and demonstrates that it is possible to anticipate the future of one of the most feared resistance genes.

An evolutive atlas for surveillance and treatment

By forcing its adaptation under clinically used antibiotics and characterizing it in detail mutation by mutation, the team reconstructed a detailed "map" of pathways that allow KPC-2 to expand its destructive repertoire, identifying multiple clinical variants and revealing its potential Achilles' heels.

The great novelty of this approach is that it can be extended to other resistance genes. Instead of waiting for dangerous variants to appear in hospitals, scientists can force them into harmless laboratory strains under controlled conditions, identify them in real time, and precisely measure their impact on resistance. The result is an evolutionary atlas that shows recurring shortcuts, high-risk combinations, and even dead ends that could be exploited with combination treatments.

Galician Alejandro Couce's line of research has sought for years to understand how to stay ahead of inevitable bacterial evolution. Last year, he surprised everyone with a study in Science that showed that the first steps of adaptation can be predicted in the laboratory. Now, he is extending that idea to the clinical field of multiple resistance. And the lesson is clear: anticipating KPC-2's moves allows us to play with an advantage, blocking its exits and keeping our best pieces alive: the antibiotics.

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